Epstein-Barr virus latent infection and BAFF expression in B cells in the multiple sclerosis brain: implications for viral persistence and intrathecal B-cell activation

J Neuropathol Exp Neurol. 2010 Jul;69(7):677-93. doi: 10.1097/NEN.0b013e3181e332ec.


A cardinal feature of multiple sclerosis (MS) is the persistent intrathecal synthesis of antibodies. Our previous finding that a large fraction of B cells infiltrating the MS brain are infected with Epstein-Barr virus (EBV) raises the possibility that this virus, because of its ability to establish a latent infection in B cells and interfere with their differentiation, contributes to B-cell dysregulation in MS. The aim of this study was to gain further insight into EBV latency programs and their relationship to B-cell activation in the MS brain. Immunohistochemical analysis of postmortem MS brain samples harboring large EBV deposits revealed that most B cells in white matter lesions, meninges, and ectopic B-cell follicles are CD27+ antigen-experienced cells and coexpress latent membrane protein 1 and latent membrane protein 2A, 2 EBV-encoded proteins that provide survival and maturation signals to B cells. By combining laser-capture microdissection with preamplification reverse transcription-polymerase chain reaction techniques, EBV latency transcripts (latent membrane protein 2A, EBV nuclear antigen 1) were detected in all MS brain samples analyzed. We also found that B cell-activating factor of the tumor necrosis factor family is expressed in EBV-infected B cells in acute MS lesions and ectopic B-cell follicles. These findings support a role for EBV infection in B-cell activation in the MS brain and suggest that B cell-activating factor of the tumor necrosis factor family produced by EBV-infected B cells may contribute to this process resulting in viral persistence and, possibly, disruption of B-cell tolerance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • B-Cell Activating Factor / metabolism*
  • B-Lymphocytes / metabolism*
  • Brain / cytology*
  • Cell Line, Transformed
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / pathology
  • Epstein-Barr Virus Nuclear Antigens / metabolism
  • Herpesvirus 4, Human / pathogenicity*
  • Humans
  • Microdissection / methods
  • Microscopy, Confocal
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / pathology*
  • Multiple Sclerosis / virology*
  • Postmortem Changes
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism


  • Antigens, CD
  • B-Cell Activating Factor
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Epstein-Barr Virus Nuclear Antigens
  • TNFSF13B protein, human
  • Viral Matrix Proteins
  • EBV-encoded nuclear antigen 1